Regulation of functions of drug transporters in renal tubules by inflammatory cytokines and implication of its significance

甲氨蝶呤（MTX）在脂多糖（LPS）诱导的炎症大鼠模型中的血浆清除率下降约50%。 LPS引起的MTX肾清除率降低与肾小球滤过和肾小管分泌有关。 在LPS大鼠中，肾组织/血浆浓度比和从肾组织到肾小管腔的外排清除率也降低，并且与肾脏中有机阴离子转运蛋白（rOAT 1、rOAT 3、rMRP 2、rMRP 4）的表达水平降低相当。 总之，MTX的肾脏清除率显着下降，在LPS处理的大鼠和肾小球滤过率下降，以及在肾小管中的有机阴离子转运蛋白的表达水平下降的贡献建议。

Plasma clearance of methotrexate (MTX) decreased about 50% in the inflammatory rat model, which is prepared by the administration of lipopolysaccharide (LPS). Involvement of glomerular filtration as well as tubular secretion were suggested in the decreased renal clearance of MTX by LPS. Renal tissue/plasma concentration ratio and efflux clearance from renal tissue to the tubular lumen also decreased in LPS rats, and were comparable to the decreased expression levels of organic anion transporters (rOAT1, rOAT3, rMRP2, rMRP4) in the kidney. In conclusion, the renal clearance of MTX markedly decreased in the LPS-treated rats and the contribution of decreased glomerular filtration as well as decreased expression levels of organic anion transporters in the renal tubules were suggested.